Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity

Objective: The insulin responsive adiponutrin or palatin-like phospholipase 3 (PNPLA 3. previously ADPN) gene shows association with obesity and in vitro adipocyte lipolysis. This study aimed to replicate the association between PNPLA3 variants and obesity. and to investigate their effect on insulin resistance and beta-cell function. Methods: rs738409 (Met148He) and rs2072907 (C to G) were genotyped using TaqMan allelic discrimination assay ill it Swedish population-based sample (n=1811). Oral glucose tolerance test (OGTT) with data from three time points (0.30 and 120 min) were available from individuals under the age of 50 years (n=973). Results: But variant alleles were associated with decreased prevalence of obesity (P < 0.05): odds ratio 0.75 (0.61-0.93) per carried Ile-allele for rs718409 and 0.80 (0.64-1.00) per carried G-allele for rs2072907. For obesity its it quantitative trait. there was no association in the whole population, but in obese subjects body mass index (BMI: P=0.023) and waist (P=0.0098) were higher in carriers off he Ile-allele. The Ile-carriers also displayed decreased insulin secretion in response to OGTT (30 min insulin: P=0.007, insulinogenic index: P=0.0051) with no significant differences in fasting plasma glucose (P=0.11). beta-cell function (disposition index: P = 0.17) or homeostasis model of assessment insulin resistance (HOMA-IR: P=0.063). The correlation between BMI and HOMA-IR differed (Met/X versus Ile/Ile. P=0.028). Met-allele carriers were seemingly more insulin resistant at a lower BMI The rs2072907 variant shows similar results for insulin secretion. The significance of this finding remained after adjusting for age, gender. Mid level of self-reported leisure-time physical activity. Conclusion: We confirm the association between PNPLA 3 and obesity addition. the rs738409 variant was associated With insulin secretion. mere seems to be it differential effect of the Ile-allele depending on the degree of obesity. possibly its it consequence Of insulin resistance..